Triptolide ameliorates fine particulate matter-induced podocytes injury via regulating NF-κB signaling pathway

Abstract

Background: PM2.5 is associated closely with an increased risk of membranous nephropathy (MN), however, whether PM2.5 could induce podocytes injury, the underlying pathology for MN, has not be thoroughly studied. Triptolide, an active component in Tripterygium wilfordii Hook F, is frequently used to treat MN in China, but its effects on PM2.5-induced podocytes injury is still largely unknown. Therefore, we evaluated the effects of PM2.5 on podocytes, and explored whether triptolide could improve PM2.5-induced podocytes injury and the possible underlying mechanisms. Results: Podocytes were incubated with PM2.5 after being pre-treated with triptolide, viability, apoptosis rate and migratory capacity of podocytes were determined by CCK-8 assay, flow cytometry and Transwell assay, respectively. Additionally, the levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), and superoxide dismutase (SOD) in podocytes, the cytoskeleton of podocytes, the protein expressions of nephrin, podocin, Bcl-2, Bax, nuclear factor kappa-B/p65 (NF-κB/p65) and phospho-inhibitor of NF-κB (p-IκBα) were measured. Our data showed that PM2.5 treatment significantly increased the disorganization of F-actin stress fibers, the damaged structural integrity of nucleus, the deranged and dissociated cytoskeleton in podocytes, increased the podocytes apoptosis rate, the levels of MDA and LDH, markedly up-regulated the protein expression of Bax, NF-κB/p65 and p-IκBα, downregulated the protein expression of nephrin, podocin and Bcl-2, and significantly decreased the level of SOD, the migration rate and the viability of podocytes, compared with those of the untreated podocytes. These effects of PM2.5 on podocytes, however, were reversed by triptolide administration. Conclusion: These results suggest that triptolide could prevent against PM2.5-induced podocytes injury via suppressing NF-κB signaling pathway.

BVD protects against UVB-induced HaCaT keratinocytes photodamage through reactivating Nrf2 antioxidative stress signaling

“…In this study, we found that BVD had a protective effect against UVB-induced photodamage. Compared with cells in the control group, after 30 mJ/cm 2 During oxidative stress, ROS and MDA are continuously being produced, and SOD is being decreased [28][29][30]. In this study, it was shown that the ROS in cells clearly increased after UV irradiation but that ROS decreased significantly in cells incubated for one hour with BVD before UV irradiation, indicating a dose-dependent correlation with BVD concentration.…”

Inhalation of Salvianolic acid B Prevents Fine Particulate Matter-Induced Acute Airway Inflammation and Oxidative Stress by Downregulating the LTR4/MyD88/NLRP3 Pathway

“…Over recent years, researchers have attempted to prevent and control the cellular and organ damage caused by PM2.5. Some researchers have shown that some natural compounds, and traditional Chinese medicines, can protect the cell and organ damage induced by PM2.5 both in vitro and in vivo, including isovitexin [21], astaxanthin [22], curcumin [23], astragalus [24], codonopsis pilosula [24], ophiopogonin [25], triptolide [26], astragaloside IV [27], resveratrol [28], and lentinan [29]. All of these studies were carried out in vivo; drugs were administered systematically, by either oral or injection routes.…”

“…An inhibitor of MyD88 (ST2825) was used consistently as a control drug for all in vivo and in vitro experiments. Previous studies have shown that PM2.5 promotes plaque vulnerability at different stages of atherosclerosis, the formation of foam cells [6], lung injury [27], and exacerbates allergic in ammation in the murine lung [30] via the TLR4/MyD88/NFκB pathway. Previous research, involving MyD88 −/− mice, showed that the exacerbation of PM2.5-enhanced ovalbumin allergic in ammation was signi cantly inhibited [31].…”

Mechanisms and Efficacy of Chinese Herbal Medicines in Chronic Kidney Disease

“…Astragaloside (Gao et al, 2012;Gui et al, 2013;Wang et al, 2014;Xu et al, 2014a;Che et al, 2015;Wang et al, 2015d;Zhou et al, 2017b;Chen et al, 2018;Du et al, 2018;Ji et al, 2018;Chen et al, 2019b;Ju et al, 2019;Qu et al, 2019;Su et al, 2019;Wang et al, 2019c), calycosin (Tang et al, 2011; Tripterygium glycoside (Wan et al, 2010;Cheng et al, 2015a;Ma et al, 2015b;Wu et al, 2017;Gong et al, 2018;Zhan et al, 2019;Wang et al, 2020), triptolide (Gao et al, 2010;Yuan et al, 2011;Ma et al, 2013;Cao et al, 2015;Zhou et al, 2016;Dong et al, 2017;Li et al, 2017c;Liang et al, 2018;Yang et al, 2019b;Wan et al, 2020), celastrol (Yu et al, 2018;Zhang et al, 2019c) Puerarin (Kim et al, 2010;Zhong et al, 2014;Pan et al, 2015;Song et al, 2016;Zhou et a...…”

“…Tripterygium wilfordii Hook. f. and its extractions, tripterygium glycoside and triptolid, have been reported to attenuate proteinuria and podocyte injury in many animal models of kidney diseases by suppression of inflammatory factors (transforming growth factor- β1 [TGF-β1], interleukin-2, and interferon-γ) ( Wan et al, 2010 ), macrophage infiltration ( Ma et al, 2013 ), oxidative stress (lactate dehydrogenase, malondialdehyde [MDA], and super oxide dismutase [SOD]) ( Wan et al, 2020 ). With prolongation of treatment time, the efficacy of triptolide increased, and the effect was better in the high-dose group than in the low-dose group ( Gao et al, 2010 ).…”